NZ242148A

NZ242148A - Emollient composition for use in therapeutic radiation treatment of psoriasis

Info

Publication number: NZ242148A
Application number: NZ242148A
Authority: NZ
Inventors: William Henry Lee
Original assignee: Bioglan Lab Ltd
Priority date: 1991-03-26
Filing date: 1992-03-26
Publication date: 1993-07-27
Also published as: CA2106065A1; JPH06507391A; KR100243758B1; GB9106365D0; DE69231628D1; EP0702568A1; AU1432992A; AU671584B2; SG49928A1; WO1992017208A1; IE920975A1; ATE198422T1; EP0702568B1; US5501849A

Abstract

PCT No. PCT/GB92/00556 Sec. 371 Date Sep. 24, 1993 Sec. 102(e) Date Sep. 24, 1993 PCT Filed Mar. 26, 1992 PCT Pub. No. WO92/17208 PCT Pub. Date Oct. 15, 1992.An emollient composition, for use in a method of treating a psoriasis in which abnormal skin is exposed to actinic or ultraviolet radiation, comprising a lipophilic emollient, wherein the composition is a non-viscous liquid which, on application to skin or a like surface, spreads to provide a substantially uniform coating of the lipophilic emollient, and wherein the coating does not absorb a significant amount of the incident actinic or ultraviolet radiation and is sufficiently non-volatile to persist for a period of sufficient length, for a therapeutically effective dose of incident radiation to be administered.

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £42148 Z 4 2 H 8 p-- , > • 2 s?. .0^ „ — : d: 26. Aft". /fte rh.c Afci .K-tfj.CSr AfeIfcus/ .Q5 r,. A.^I .^/UrO PubliTtiti:i L 2/ JUL 1993 P.O. J i,ic: ..J.'^.a NO DRAWING! Patents Form No. 5 Number PATENTS ACT 1953 Dated COMPLETE SPECIFICATION AN EMOLLIENT COMPOSITION We, BIOGLAN LABORATORIES LIMITED, a UK company, of 1, The Cam Centre, Wilbury Way, Hitchin, Hertfordshire SG4 OTW, England do hereby declare the invention for which we pray that a Patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: 24 21 - la- This invention relates to an emollient for use in a method of treating a dermatological disorder in which the abnormal skin is exposed to Ultraviolet light (UV), 10 preferably to UVA. In particular, emollients in accordance with the present invention are useful in treating skin disorders, such as psoriasis, in which the stratum corneum becomes flakey, or scaly. 15 Psoriasis has been treated successfully by irradiating effected areas of skin with ultraviolet light, since this method was first proposed by Goeckerman (North West Med, 24: 229-2 31, 1925). The original Goeckerman regime requires the effected area to be topically 20 treated with crude coal tar, the subsequent removal of the crude coal tar with olive oil, followed by irradiation of the area with ultraviolet light from a *"> -V" ;24? i ;- 2 - ;medium pressure mercury discharge lamp. In a modern development of this original therapy, known as PUVA treatment, a psoralen, such as trimethylpsoralen, or 8-methoxypsoralen is administered, either systemically 5 or topically to the effected area and the effected area is subsequently irradiated with UVA radiation. The PUVA treatment appears to be a most effective treatment for psoriasis and has been in use since first being described in 1974 (Parrish et.al. New England Journal 10 of Medicine, Vol. 29, No.23, 1974). Also some good results have been achieved by irradiating psoriatic plaques, coated with an emollient, with UVB (See Fischer, Acta Dermatovener (Stockh)56; 473-479, 1976). ;15 In both PUVA and other similar treatments, it has been a common practice to coat the skin with an emollient prior to treatment, in order to ensure that diseased areas of skin receive a sufficient dose of radiation, while preventing the skin from flaking and 20 suffering localised buring. There are numerous air spaces between the abnormal corneocytes in dry psoriatic plaques and, accordingly, if no emollient is used, incident ultraviolet radiation must pass through ;-!/ ;2 4 ?. 1 4 8 ;many air/skin boundries, before impinging upon the epidermis below, where it may have a therapeutic effect. At each air/skin boundry a certain amount of light is reflected and, thus, the many such boundries 5 present in dry psoriatic skin can reflect a significant amount of radiation. The effect of an emollient is to fill these air spaces and to render the scales of skin translucent by decreasing the reflection of incident ultraviolet light. It has been shown that the 10 transmission of ultraviolet light through psoriatic plaques can be increased between 2 and 3 times by the use of an emollient (see Leroy et.al. Photo dermatol 3, 1986, 51-52; J.A. Parrish Phototherapy of Skin diseases and; R.R. Anderson and J.A. Parrish, the Optics of 15 Human Skin, J. Invest. Dermatol. 1981; 77: 13-19.). ;In this way, the transmission properties of psoriatic plaques can be rendered similar to that of a normal stratum corneum and the therapeutically effective dose 20 of radiation can be reduced to a level less likely to be harmful (by way of causing painful erythema or burning) to normal skin, which it is often impossible to avoid irradiating when earring out PUVA or like ;24214 ;treatments. Thus, an emollient can prevent damage to normal skin, while allowing a therapeutically effective dose of radiation to be given to adjacent diseased areas. ;5 ;The emollients employed up to date in PUVA therapy and phototherapy using UVB, all absorb a certain amount of ultraviolet light and, thus, reduce the amount of such radiation that reaches the epidermis (this effect is ;10 usually outweighed by the previously discussed enhancement of transmission through scaly skin.). In order to overcome this difficulty, patients can be exposed to radiation for longer periods, or to higher intensities of radiation, in order to provide a ;15 therapeutic dose of radiation. In theory, this practice should not increase the amount of radiation penetrating skin coated with an emollient. ;Where the effected areas of skin are extensive, it is 20 common practice for a sufferer's entire body to be irradiated, in a light cabinet, after an appropriate emollient has been applied to all exposed areas of skin. ;9 L ?. 1 4 ;A well documented harmful side effect of exposure to ultraviolet light is that, after significant periods of exposure, skin cancers can be developed. For this reason, PUVA treatment and phototherapy with UVB tend 5 to be used on older individuals, whose life expectancy is generally shorter than the period required for most skin cancers to develop at the level of exposure to radiation which their treatment involves. The use of emollients has allowed the exposure to radiation during 10 PUVA treatment to be reduced, without reducing the efficacy of the treatment, and, therefore, has allowed younger patients to enjoy the benefits of the treatment. However, further reductions in the amount of UV exposure required would reduce still further any 15 cancer risk as well as the amount of erythema caused by PUVA treatment. ;According to a first aspect of the present invention there is provided an emollient composition, for use in 20 a method of treating a dermatological disorder in which abnormal skin is exposed to incident therapeutic radiation, comprising a lipophilic emollient, wherein the composition is a non-viscous liquid which, on ;n / r A ;/ u / \ ;application to skin or a like surface, spreads to provide a substantially uniform coating of the lipophilic emollient, and the wherein coating does not absorb a significant ainount of the incident therapeutic 5 radiation and is sufficiently non-volatile to persist for a period of sufficient length, for a therapeutically effective dose of incident radiation to be administered. Thus, the emollient composition can include a relatively non-volatile lipophilic emollient, 10 which does not absorb a significant amount of the incident therapeutic radiation. Preferably, the incident therapeutic radiation is of a wavelength within the broad band UV, UVA, or UVB regions of the electromagnetic spectrum. ;15 ;In an embodiment, the lipophilic emollient is chosen so that a 5nm layer thereof absorbs 20% or less and, preferably, 10% or less of the incident therapeutic radiation. Preferably, a 5tim layer of the 20 lipophilic emollient absorbs 20% or less and, more preferably, 10% or less incident radiation at any wavelength within the broad band UV, UVA or UVB regions of the electromagnetic spectrum. ;24214 ;In embodiments, the composition can comprise a non-volatile and relatively thick lipophilic emollient dissolved in a non-viscous, volatile and non-polar solvent. ;5 ;In this specification broad band UV is defined as radiation of a wavelength between 285 and 400 nm, UVA has a wavelength of 320-400 nm and UVB a wavelength of 285-320 nm. ;10 ;When an emollient in accordance with the present invention is employed in a PUVA or like treatment, the amount of ultraviolet radiation required to have a therapeutic effect on scaly skin is reduced, in much 15 the same way as it is when conventional emollients are employed. Thus the radiation dose received by adjacent normal skin, which has been coated with the emollient, can be held to a less harmful level, as is achievable when using conventional emollients. ;20 ;However, because the coating of the lipophilic emollient, produced on skin by a composition in accordance with the present invention, absorbs less UV ;242 1 4 ;- 8 - ;than would a conventional non-volatile emollient, the overall amount of radiation required in order to achieve a therapeutic effect is reduced. Since compositions of the present invention are non-viscous, after application to the skin, they leave a thin and highly uniform layer of the lipophilic emollient on the skin, in contrast to the more viscous conventional emollient compositions which are difficult to apply in a consistantly uniform thickness. The thinness of the layer of emollient left on the skin by a composition in accordance with the present invention allows the amount of UV requird to achieve a particular UV dose to the skin to be reduced still further. Although this has little, or no effect on the UV dose received by areas coated in emollient (because the dose of incident radiation is reduced in compensation for reduced absorption by the emollient), areas of skin which have been accidentally left uncoated and areas which cannot be coated, such as the eyes and lips, will receive a lower dose of ultraviolet radiation. As a result, the overall risk of causing cancer, ocular side effects and painful erythema is reduced by using a composition in accordance with the present invention. Thus, contrary ;24 214 ;to initial expectations, an emollient which absorbs very little UV is safer in use than one whose absorption is significant. Also, being non-viscous, a composition in accordance with the present invention ;5 flows readily and, thus, is easy to apply without leaving gaps of uncoated skin. However, because the lipophilic emollient is non-volatile, it remains present on the skin for long enough for treatment to be completed. ;10 ;Preferably, after application to healthy normal the emollient transmits through to the skin 90% and, more preferably, 95% or more incident UVA, ;broad band UV. ;15 ;The preferred incident therapeutic radiation is within the UVA region of the electromagnetic spectrum, and the method of treatment is preferably a PUVA treatment. ;skin, or more UVB or ;20 In a preferred embodiment the composition has a viscosity of between 5 and 20,000 centipoise and, preferably, a viscosity of between 5 and 2,5000 centipoise. Preferably, the lipophilic emollient has a ;24214 ;- 10 - ;partial vapour pressure of 17.5mmHg, or less, and, preferably, lOmmHg, or less, at 20°C. Also, it is preferred that the partial vapour pressure of a coating, formed by the composition on skin or like surface, 5 should be 17.5mmHg, or less, and preferably, lOmmHg, or less, at 20°C, for a period of sufficient length for a therapeutically effective dose of incident radiation to be administered. ;10 In a preferred form, the inventive composition further comprises a carrier for the lipophilic emollient. The carrier functions to cause the lipophilic emollient to spread into a thinner and/or more uniform coating on skin and, therefore, can allow thick or solid lipophilic 15 emollients to be employed. Also, the carrier can cause the composition to creep across a surface and, thus, ensures that an even unbroken coating of lipophilic emollient is produced. Preferably, the carrier comprises a substantially apolar solvent which can be 20 cyclomethicone, octamethylcyclotetrasiloxane, ;decamethylcyclopentasiloxane, a dimethicone, or a mixture of any of these and, preferably, is cyclomethicone. ;\ i} 12 ;2421 ;- ii - ;In further embodiments the carrier comprises a surfactant, which can be isopropylisostearate, pentaerythratol tetraisostearate, promyristyl propionate, myristyl lactate, oleyl erucate, isopropyl 5 myristate, isocetyl stearate, or a mixture of any of these and, preferably, is isopropylisostearate. The surfactant can be used together with an apolar solvent, to form the carrier. ;10 The lipophilic emollient, preferably, is coconut oil, sesame oil, suflower oil, corn oil, a mineral oil such as liquid paraffin or a fraction thereof, any other like saturated oil or, a mixture of any of these, and, more preferably, is coconut oil. ;15 ;In a preferred embodiment the composition is formulated to be suitable for spray application. When so formulated the composition can be sprayed on to the skin to rapidly coat the latter with a substantially 20 uniform film of the emollient. The emollient can be a modified coconut oil. ;\? !* - 12 - In a second aspect of the present invention there is provided a spray applicator, filled with a composition in accordance with the present invention. Advantageously, such an applicator provides a highly 5 convenient means of applying the composition, prior to treatment with ultraviolet light. The dermatological disorders to which the present invention is applicable include those which result in 10 scaly formations in the stratum corneum. The most preferred disorder is psoriasis. In a most preferred embodiment of the present invention, a substance effective in stimulating 15 melanocytes to produce melanin is included in the composition. This substance, preferably, is a psoralen or urocanic acid. Also, a psoralens can be administered, either systemically or topically, prior to irradiation with ultraviolet light. Preferably the 20 psoralen is included in the composition and is 8-methoxypsoralen or trimethylpsoralen and is included in a concentration of between 0.1% and 10% by weight. 9 b, 9 1 4 - 13 - In a preferred form, which includes a surfactant, the latter increases the spreadability of the lipophilic emollient and assists the emollient's penetration of the stratum corneum. When an apolar solvent is used, 5 it reduces the oiliness and viscosity of the composition, so that a uniform and thin film of emollient remains on the skin after application. In such an embodiment the preferred emollient is coconut oil. Natural coconut oil melts at around room 10 temperature and, thus, is difficult to apply to the body. When formulated in the aformentioned manner, the oil may be sprayed on without difficulty. Most preferably, the composition comprises coconut oil, Isopropylisostearate and cyclomethicone. 15 Examples of emollient compositions in accordance with the present invention are set out in Examples 1 and 2. Example 1 20 Composition A 100 grams of natural coconut oil is blended with 100 grams of Isopropylisostearate and 100 grams of cyclomethicone, to provide a non-viscous liquid ? A ? 1 4 - 14 - composition. The liquid is packaged in equal 50 gram portions in six 100 ml capacity pump action spray cannisters. 5 Example 2 Composition B A non-viscous liquid composition was made up from the same constituents and in the same quantities as described in Example 1. To this composition, 15 grams 10 of 8-methoxypsoralen was added and dissolved therein. The resulting solution was packaged in pump action spray cannisters, in the manner described in Example 1. Examples of the use of Compositions A and B are set out 15 below. Example 3 Prior to treatment with UVA a patient suffering from psoriasis should receive a therapeutically effective 20 dose of trimethylpsoralen or 8-methyoxypsoralen. If the latter is used, it may be administered orally, at a dose of about 0.6 mg/Kg body weight. After two hours and immediately before treatment, a patient's body 9k9 - 15 - should be sprayed with a uniform layer of composition A. The composition is easily applied and tends to spread to cover any gaps or areas of light application. 5 Once coated in emollient, the patient undergoes UVA treatment for between 2 and 5 minutes in a conventional UVA light cabinet, after which the emollient may be washed off. Treatment normally involves 2-3 such exposures for 4-8 weeks, until the diseased areas have 10 reverted substantially back to normal. Thereafter, the disease may be held in check by a maintenance regime of 1 PUVA treatment per week over an indefinite period. Example 4 15 Use of Composition B A patient suffering from extensive psoriasis should be sprayed over his entire body with a uniform layer of composition B. As with composition A, composition B is 20 easily applied and tends to spread to cover any gaps or areas of light application. However, unlike when using composition A, it is not necessary for a separate dose of a psoralens to be given and, accordingly, the </div>

Claims

<div class="application article clearfix printTableText" id="claims"> n n n M ' ' i - 16 - patient may enter the UVA light cabinet shortly after being sprayed with composition B. It may be necessary for the patient to wait a while before entering the light cabinet, in order to allow sufficient of the 5 8-methoxypsoralen to be absorbed into the epidermis. The treatment regime is the same as set out in Example 3, i.e. 2-3 exposures to UVA per week for 4-8 weeks, followed by a maintenance regime of 1 PUVA treatment per week. 10 Whole body light cabinets which are suitable for use in the manner set out in either Example 3 or 4 are listed in P.J. Mounford, "Phototherapy and PhotoChemotherapy Ultraviolet Irradiation Equipment", Photodermatology 15 1986:3:83/91. The exact exposure times for each particular light cabinets should be determined by a responsible clinician in the normal manner. * * \ n \ , t . j v ■*- n, 0 1 -- - 17 WHAT WE CLAIM IS:

1. An emollient composition, for use in a method of 5 treating psoriasis in which abnormal skin is exposed to incident therapeutic radiation, comprising a lipophilic emollient and an active agent, wherein the active agent is trimethylpsoralen, 8-methoxypsoralen or urocanic acid and the composition is a non-viscous liquid which, on 10 application to skin or a like surface, spreads to provide a substantially uniform coating of the lipophilic emollient and active agent, and wherein the coating does not absorb a significant amount of the incident therapeutic radiation and is sufficiently 15 non-volatile to persist for a period of sufficient length, for a therapeutically effective dose of incident radiation to be administered.

2. An emollient composition, for use in a method 20 of treating psoriasis in which abnormal skin is exposed to incident broad band UV, UVA or UVB radiation, comprising a lipophilic emollient, wheire'in'the r \ 2'hay 19sb 24 ^ 1 !> - is - composition is anhydrous, has a viscosity of between 5 and 2500 centipoise and, on application to skin or a like surface, spreads to provide a substantially uniform coating of the lipophilic emollient which, when 5 spread in a 5nm layer, absorbs 10% or less of the incident therapeutic radiation, has a partial vapour pressure of 10 mmHg or less, at 20°C, and is sufficiently non-volatile to persist for a period of sufficient length, for a therapeutically effective dose 10 of incident radiation to be administered.

3. An emollient composition as claimed in claim 1, wherein the incident therapeutic radiation is of a wavelength within the broad band UV, UVA, or UVB 15 regions of the electromagnetic spectrum.

4. An emollient composition, as claimed in claim 1 or claim 3, wherein a 5(im layer of the lipophilic emollient absorbs 20% or less and, preferably, 10% or 20 less of the incident therapeutic radiation. 3 i May I99.X 2*21*8 - 19 -

5. An emollient composition as claimed in claim 1, 3 or 4 wherein a 5nm layer of the lipophilic emollient absorbs 20% or less and, preferably, 10% or less incident radiation at any wavelength within the 5 broad band UV, UVA or UVB regions of the electromagnetic spectrum.

6. An emollient composition, as claimed in any of claims 1 and 3-5, having a viscosity of between 5 and 10 20,000 centipoise and, preferably, a viscosity of between 5 and 2,500 centipoise.

7. An emollient composition, as claimed in any of claims 1 and 3-6, wherein the lipophilic emollient has 15 a partial vapour pressure of 17.5mmHg, or less, and, preferably, lOmmHg, or less, at 20°C. 8. An emollient composition as claimed in any of claims 1 and 3-7, wherein the partial vapour pressure 20 of a coating, formed by the composition on skin or a like surface, is 17.5mmHg, or less, and, preferably, lOmmHg, or less, at 20°C, for a period of \ - 20 - sufficient length for a therapeutically effective dose of incident radiation to be administered. 9. An emollient composition, as claimed in any of 5 claims 1-8, further comprising a carrier for the lipophilic emollient. 10. An emollient composition as claimed in claim 9, wherein the carrier comprises a substantially apolar 10 solvent. 11. An emollient composition, as claimed in claim 10, wherein the apolar solvent is cyclomethicone, octamethylcyclotetrasiloxane, decamethylcyclo-15 pentasiloxane, a dimethicone, or a mixture of any of these and, preferably, is cyclomethicone. 12. An emollient composition, as claimed in any of claims 9-11, wherein the carrier comprises a 20 surfactant. 24 2 1 4 S - 2! - 13. An emollient composition as claimed in claim 12, wherein the surfactant is isopropylisostearate, pentaerythratol tetraisostearate, promyristyl propionate, myristyl lactate, oleyl erucate, isopropyl 5 myristate, isocetyl stearate, or a mixture of any of these and, preferably, is isopropylisostearate. 14. An emollient composition, as claimed in any of the preceding claims, wherein the lipophilic emollient 10 is coconut oil, sesame oil, sunflower oil, corn oil, a mineral oil such as liquid paraffin or a fraction thereof, any other like saturated oil or, a mixture of any of these, and, preferably, is coconut oil. 15 15. An emollient composition, as claimed in claim 2, further comprising a substance effective in stimulating melanocytes to produce melanin. 16. An emollient composition, as claimed in claim 15, 20 wherein said substance is trimethylpsoralen,

8-methoxypsoralen, or urocanic acid. ' ^ > E . • 1 0\s -\ •jy 3 I MAY 1993 - 22 - 17. An emollient composition, as claimed in any of claims 1 and 3-14 or 16, wherein said trymethylpsoralen, or 8-methoxypsoralen is present in a concentration of between 0.1 and 10% by weight. 18. An emollient composition, as claimed in any of claims 1-17, wherein the incident therapeutic radiation is within the UVA region of the electromagnetic spectrum. 19. The use of a composition, as claimed in any of the preceding claims, for the preparation of a medicament for use in a method of treating psoriasis, in conjunction with ultraviolet radiation, preferably, in the UVA region. 20. A spray applicator filled with a composition, s claimed in any of claims 1-18. ' <■ r* />•. - !', 3 WE ST-V7A L.'CJiR, McCABE por: v::V-\kv:vV.< ^ ATTORNEYS FO,-i THE APPLICANT i 1 MAY 1993 $ I v </div>